Differential dose-dependent effects of alpha-, beta-carotenes and lycopene on gap-junctional intercellular communication in rat liver in vivo.
In order to examine the relevance of alteration of gap-junctional intercellular communication (GJIC) to chemopreventive activity against carcinogenesis, the effects of alpha- and beta-carotene as well as lycopene, typical chemopreventive carotenoids, on cell coupling via gap junctions in rat liver in vivo were studied using a direct functional dye-transfer technique. We found that all three test compounds given at a dose of 50 mg/kg-body weight (b.w.) daily, 5 times by gavage, inhibited GJIC, while similar treatment with 5 mg/kg b.w. caused enhancement, especially in the beta-carotene- and lycopene-treated groups. At the dose level of 0.5 mg/kg b.w., the three compounds had no effect. The findings show that all three agents differentially modulate GJIC depending on the dose, with beneficial effects on cell communication only detected at the one dose. The result suggests that determination of the dose of chemicals to be used is crucial for human intervention studies.
Krutovskikh
V
V
Chemotherapy Division, National Cancer Center Research Institute, Tokyo.
Asamoto
M
M
Takasuka
N
N
Murakoshi
M
M
Nishino
H
H
Tsuda
H
H
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D000077276:Lycopene; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D019207:beta Carotene / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D019207:beta Carotene; D002338:Carotenoids; C041635:alpha-carotene; D000077276:Lycopene